This group of interlocking cooperative projects proposes to study the molecular mechanisms related to a number of devastating human conditions which have as their central feature an association with the human major histocompatibility complex. Both serologic, cellular, biochemical and molecular biological approaches will be used by a group of investigators to analyze at both the fundamental and clinical levels the role of HLA encoded gene products in the pathgenesis of various human diseases. Core facilities are requested in order to centralize resources and technology and to more efficiently utilize personnel and funds. Each of the individual projects follows directly from the laboratory to the clinic and back to the research laboratory and should provide important insights into the pathogenesis of human disease.